There exists at present no satisfactory biochemical technique for the early recognition of incipient of overt thrombotic state in man or animal. Thromboembolic disease is becoming an increasingly important cause of disability and death as advances in surgical procedures open way to more extensive surgery, and the wide use of estrogen containing compounds as oral contraceptives.
In recent years much experimental data both in vitro and in vivo have appeared in the literature suggesting that the efficacy of XaI as a naturally occurring anticoagulant during blood coagulation is dependent more upon its inactivation of initially generated Factor Xa thereby preventing thrombin formation, rather than preventing thrombin from attacking fibrinogen. This view is especially strengthened by the report that trace amounts of heparin could markedly enhance the inhibition of Factor Xa by XaI.
Certain circumstantial evidence strongly suggests that during and post surgery, a state of the so-called "hypercoagulability" previously absent, is created in some patients. But this hypercoagulable state will remain non thrombonic as long as the rate of Factor Xa removal by XaI exceeds that of Factor Xa formation. It has also been claimed that women on oral antiovulatory agents are more prone to thrombose as a result of injury because of lowering in their blood of XaI.
This information has raised the possibility that low levels of XaI may reflect hypercoagulability. Therefore it may be suggested that plasma XaI activity might be a practical marker of hypercoagulable state. This hypothesis is further strengthened by the following observations:
(A) PATIENTS CONGENITALLY DEFICIENT IN ANTITHROMBIN III (XaI) are thrombophilic,
(B) Women on oral contraceptive agents who have low XaI activity in their plasma, as a group, have a higher incidence of post operative deep vein thrombosis, than those who are not on the "pill".
Therefore there is a great need for a specific method of determining the biological activity of XaI in blood plasma.
There are some methods available which try to determine the XaI activity. The most frequently used methods are based upon immunological determination and the inhibition of thrombin. However these techniques have several disadvantages. Thus, the immunological method, although it will detect the antigen .alpha..sub.2 -globulin does not indicate this inhibitor's biological activity. It has been reported that certain patient's blood, congenitally deficient in this inhibitor's biological activity, showed no defiency as measured by the immuno assay. (Sas et al., Thromb. Diath. Haemorrh. 32 (1974) p. 105).
The thrombin method for this inhibitor is not specific because at the same time it measures the activity of other serum proteinase inhibitors. (Whigham et al. Thromb. Diath. Haemorrh. 34 (1975) p. 365). Moreover it is sensitive to very small amounts of heparin and heparin-like substances and fibrinogen degradation products present in the blood plasma.